Thromboxane A2 receptor mediated activation of the mitogen activated protein kinase cascades in human uterine smooth muscle cells
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|Title:||Thromboxane A2 receptor mediated activation of the mitogen activated protein kinase cascades in human uterine smooth muscle cells||Authors:||Miggin, Sinead M.
Kinsella, B. Therese
|Permanent link:||http://hdl.handle.net/10197/3163||Date:||28-May-2001||Abstract:||Both thromboxane (TX) A2 and 8-epi prostaglandin (PG) F2alpha have been reported to stimulate mitogenesis of vascular smooth muscle (SM) in a number of species. However, TXA2 and 8-epiPGF2alpha mediated mitogenic signalling have not been studied in detail in human vascular SM. Thus, using the human uterine ULTR cell line as a model, we investigated TXA2 receptor (TP) mediated mitogenic signalling in cultured human vascular SM cells. Both the TP agonist U46619 and 8-epiPGF2alpha elicited time and concentration dependent activation of the extracellular signal regulated kinase (ERK)s and c-Jun N-terminal kinase (JNK)s in ULTR cells. Whereas the TP antagonist SQ29,548 abolished U46619-mediated signalling, it only partially inhibited 8-epiPGF2alpha mediated ERK and JNK activation in ULTR cells. Both U46619 and 8-epiPGF2alpha induced ERK activations were inhibited by the protein kinase (PK) C, PKA and phosphoinositide 3-kinase inhibitors GF 109203X, H-89 and wortmannin, respectively, but were unaffected by pertussis toxin. In addition, U46619 mediated ERK activation in ULTR cells involves transactivation of the EGF receptor. In humans, TXA2 signals through two distinct TP isoforms. In investigating the involvement of the TP isoforms in mitogenic signalling, both TPalpha and TPbeta, independently directed U46619 and 8-epiPGF2alpha mediated ERK and JNK activation in human embryonic kidney (HEK) 293 cells over-expressing the individual TP isoforms. However, in contrast to that which occurred in ULTR cells, SQ29,548 abolished 8-epiPGF2alpha mediated ERK and JNK activation through both TPalpha and TPbeta in HEK 293 cells providing further evidence that 8-epiPGF2alpha may signal through alternative receptors, in addition to the TPs, in human uterine ULTR cells.||Funding Details:||Health Research Board||Type of material:||Journal Article||Publisher:||Elsevier||Journal:||Biochimica et Biophysica Acta (BBA) - Molecular Cell Research||Volume:||1539||Issue:||1-2||Start page:||147||End page:||162||Copyright (published version):||2001 Elsevier B.V.||Keywords:||Thromboxane A2 receptor; TPalpha; TPbeta; 8-epiPGF2alpha; Smooth muscle; MAPK; ERK; JNK; Mitogenesis||Subject LCSH:||Thromboxanes
Mitogen-activated protein kinases
|DOI:||10.1016/S0167-4889(01)00103-3||Other versions:||http://dx.doi.org/10.1016/S0167-4889(01)00103-3||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Conway Institute Research Collection|
Biomolecular and Biomedical Science Research Collection
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